Recently there has been a considerable increase in our knowledge concerning the control of bone resorption and bone formation by hormones and growth factors. A number of systemic growth factors such as Epidermal Growth Factor (EGF) and Platelet Derived Growth Factor (PDGF) have been shown to affect bone metabolism. However, our understanding of the factors regulating bone resorption and formation is still incomplete. Transforming Growth Factors (TGFs) are a family of recently discovered polypeptide growth factors, which have some of the biological properties of EGF. We have found that partially purified preparations of TGFs are potent stimulators of bone resorption in vitro. The aim of this proposal is to characterize fully the effects of purified TGFs as well as synthetic and recombinant TGF on bone resorption and bone formation in vitro. Bone resorption is assessed by measuring 45Ca release from previously labelled fetal rat long bones and neonatal mouse calvariae. Bone formation is assessed by measuring DNA and collagen synthesis and alkaline phosphatase activity produced by fetal rat calvariae and by cultures of isolated bone cells (both rat osteosarcoma cells and isolated human bone cells with the osteoblast phenotype). The mechanism of action of these factors will be studied using inhibitors of prostaglandin biosynthesis, phosphodiesterase inhibitors and antisera to the EGF receptor. These studies will document the effects of this important family of growth factors on bone metabolism and may help to give clearer understanding of the role of these factors in bone resorption and formation under physiological and pathological conditions.